Sorafenib and Fulvestrant in Treating Patients With Locally Advanced or Metastatic Breast Cancer That Did Not Respond to Aromatase Inhibitor Therapy

NCT00722072 | Terminated Phase 2 Results

• 5 other identifiers: IRB00004318P30CA069533OHSU-4318BAYER-OHSU-4318CDR0000601002
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

RATIONALE: Sorafenib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor. Estrogen can cause the growth of breast cancer cells. Hormone therapy using fulvestrant may fight breast cancer by blocking the use of estrogen by the tumor cells. Giving sorafenib together with fulvestrant may kill more tumor cells. PURPOSE: This phase II trial is studying how well giving sorafenib together with fulvestrant works in treating patients with locally advanced or metastatic breast cancer that did not respond to aromatase inhibitor therapy.

Conditions

Breast Cancer

Keywords

male breast cancer; stage IIIA breast cancer; stage IIIB breast cancer; stage IIIC breast cancer; stage IV breast cancer; recurrent breast cancer

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Progression-free Survival at 4 Months

  Progression-free survival rate is defined as the proportion of subjects who are progression free (CR, PR and SD) at 4 months after initiating treatment with sorafenib plus fulvestrant. Complete Response (CR):Disappearance of all target (both measurable and evaluable)lesions. Partial Response (PR):At least a 30% decrease in the sum of the longest diameter (LD) of both measurable and evaluable target lesions. Stable Disease (SD):Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease(PD).

  4 months after initiating treatment with sorafenib plus fulvestrant.

Secondary Outcomes (4)

• Objective Response Rate

  Every 8 weeks (two cycles) while receiving study therapy.

• Time to Progression

  Start of treatment to time of progression.

• Progression-free Survival

  Start of treatment to time of progression or death, whichever comes first.

• Overall Survival

  28 to 56 days after discontinuation of study therapy

Study Arms (1)

Fulvestrant/ Sorafenib

EXPERIMENTAL

Fulvestrant: A loading dose will be administered intramuscularly to all subjects during cycle 1 of treatment as follows: * 500 mg IM on Day 1 * 250 mg IM on Day 15 Upon completion of the loading dose, a fixed dose of Fulvestrant 250 mg IM will be administered on day 1 of the next 28 day cycle and every consecutive cycle until tumor progression or unacceptable toxicity occurs requiring discontinuation. Sorafenib: Subjects will take Sorafenib 800 mg/day administered as 400 mg bid (twice daily)each morning and evening approximately 12 hours apart. Treatment will begin on Day 1 of the study and continue daily until tumor progression or until unacceptable toxicity occurs.

Drug: fulvestrant; Drug: sorafenib tosylate

Interventions

fulvestrant DRUG

Loading dose for cycle 1: 500 mg intramuscular(IM) on Day 1;250 mg IM on Day 15 Upon completion of the loading dose, a fixed dose of fulvestrant 250 mg IM will be administered on day 1 of the next 28 day cycle and every consecutive cycle until tumor progression or until unacceptable toxicity occurs requiring discontinuation of study therapy

Fulvestrant/ Sorafenib

sorafenib tosylate DRUG

Subjects will take sorafenib 800 mg/day administered as 400 mg bid (twice daily) each morning and evening approximately 12 hours apart. Treatment will begin on Day 1 of the study and continue daily until tumor progression or until an unacceptable toxicity occurs which would require delay, modification or discontinuation of study therapy

Fulvestrant/ Sorafenib

Eligibility Criteria

• Age: 18 Years - 120 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

DISEASE CHARACTERISTICS: * Diagnosis of incurable breast cancer * Locally advanced or metastatic disease * Measurable or evaluable disease * Measurable disease is defined as ≥ 1 uni-dimensionally measurable lesion ≥ 20 mm by conventional techniques or ≥ 10 mm by spiral computed tomography(CT) scan * Bone-only metastases that can be imaged with bone scan AND magnetic resonance imaging (MRI) or bone scan AND plain x-ray is considered measurable disease * Tumor lesions that are situated in a previously irradiated area are considered measurable only if they are progressing at the time of study entry * Evaluable disease includes unresectable skin/chest wall metastases that can be photographed and whose size can be measured with a ruler * Bone-only metastases that can only be imaged using bone scan or malignant pleural effusion(s) only are not considered evaluable disease * Previously treated with a third-generation aromatase inhibitor (e.g., letrozole, anastrazole, or exemestane) AND meets one of the following criteria: * Progressed during palliative aromatase inhibitor therapy * Recurred during adjuvant aromatase inhibitor therapy * Recurred within 12 months of completing adjuvant aromatase inhibitor therapy * Human Epidermal growth factor Receptor 2(HER2/neu)-negative tumor * No Human Epidermal growth factor Receptor 2(HER2/neu) overexpression (i.e., tumor staining 3+ by immunohistochemistry \[IHC\] or gene amplified by Fluorescence In Situ Hybridization \[FISH\]) * Hormone receptor status: * Estrogen receptor and/or progesterone receptor positive, defined as ≥ 10% of malignant cells with positive nuclear staining PATIENT CHARACTERISTICS: * Postmenopausal * Eastern Cooperative Group(ECOG) performance status 0-1 * Life expectancy ≥ 16 weeks * Neutrophil count ≥ 1,500/mm\^³ * Platelet count ≥ 100,000/mm\^³ * Hemoglobin ≥ 9.0 g/dL * Creatinine \< 2 mg/dL * Total bilirubin ≤ 1.5 times upper limit of normal (ULN) * Alanine aminotransferase (ALT) and aspartate aminotransferase(AST) ≤ 2.5 times ULN (≤ 5 times ULN for patients with liver involvement) * International Normalized Ratio(INR) \< 1.5 OR Prothrombin time/ partial thromboplastin time (PT/PTT) normal * Left ventricular ejection fraction(LVEF) normal by Multiple Gated Acquisition(MUGA) or ECHO * No known allergy to sorafenib tosylate or fulvestrant * No cardiac disease, including any of the following: * New York Heart Association(NYHA) class III-IV congestive heart failure * Unstable angina (anginal symptoms at rest) or new-onset angina (within the past 3 months) * Myocardial infarction within the past 6 months * Cardiac ventricular arrhythmias requiring anti-arrhythmic therapy * No uncontrolled hypertension, defined as systolic blood pressure \> 150 mm Hg or diastolic blood pressure \> 90 mm Hg despite optimal medical management * No thrombotic or embolic events, such as cerebrovascular accident (including transient ischemic attacks), within the past 6 months * No known HIV infection or chronic hepatitis B or C infection * No infection that requires IV antibiotics or produces a fever \> 100°F within the past 72 hours * No pulmonary hemorrhage/bleeding event ≥ Common terminology criteria for adverse events(CTCAE) grade 2 within the past 4 weeks * No other hemorrhage/bleeding event ≥ CTCAE grade 3 within the past 4 weeks * No evidence or history of bleeding diathesis or coagulopathy * No significant traumatic injury within the past 2 weeks * No serious, nonhealing wound, ulcer, or bone fracture * No condition that impairs the patient's ability to swallow whole pills * No malabsorption problem * No second malignancy within the past 5 years, except adequately treated and cured basal cell or squamous cell skin cancer or carcinoma in situ of the cervix * No underlying medical condition that, in the principal investigator's opinion, will make the administration of study drug hazardous or would obscure the interpretation of adverse events PRIOR CONCURRENT THERAPY: * See Disease Characteristics * No prior chemotherapy for metastatic or unresectable locally advanced breast cancer * No prior sorafenib tosylate or other Vascular endothelial growth factor(VEGF)-targeting therapies * More than 2 weeks since prior major surgery or open biopsy * No concurrent anticoagulation with warfarin or heparin * No concurrent Hypericum perforatum (St. John wort) or rifampin * No other concurrent anticancer agents, including chemotherapy or biological therapy * No other concurrent investigational drugs * Concurrent bisphosphonates allowed

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• OHSU Knight Cancer Institute: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

OHSU Knight Cancer Institute

Portland, Oregon, 97239-3098, United States

Location

MeSH Terms

Conditions

Breast Neoplasms; Breast Neoplasms, Male

Interventions

Fulvestrant; Sorafenib

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Estradiol; Estrenes; Estranes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Estradiol Congeners; Gonadal Steroid Hormones; Gonadal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Phenylurea Compounds; Urea; Amides; Organic Chemicals; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Niacinamide; Nicotinic Acids; Acids, Heterocyclic; Heterocyclic Compounds; Pyridines; Heterocyclic Compounds, 1-Ring

Results Point of Contact

• Title: Dr. Stephen Chui
• Organization: OHSU Knight Cancer Institute

chuis@ohsu.edu

503-494-8534

Study Officials

• Stephen Chui, MD

  OHSU Knight Cancer Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 24, 2008
• First Posted: July 25, 2008
• Study Start: July 1, 2008
• Primary Completion: July 1, 2010
• Study Completion: July 1, 2012
• Last Updated: February 26, 2018
• Results First Posted: September 5, 2011

Record last verified: 2018-01

Locations

US (1)